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Author
Topic: Can Resistance Still Occur Even With 100% Adherence? (Read 27491 times)

What it all boils down to is that each and every one of our structures are different. Facts are based on past happenings and present potentials. What is good for Jimmy aint always doin it for Joey. I have been on meds for a year. I have never missed a dose, and not even by more than an hour and a half. I have been undetectable since my very first screening after a VL of over a million.

I will continue to take those meds as long as they work. I started a thread on a lab fuck up that showed me at 92,000. Thank god it wasn't correct, but I was making plans for a new cocktail. I will do whatever I have to do.

But it was the best we had back in 1996 and it works. In July, I will have been undetectable for 10 years.

That is, if my viral load is still undetectable. There are no guarantees.

As Tim (Moffie) said, I believe the answer to the original question is yes, the virus will eventually mutate and force me to switch my regimen.

Have I been 100 percent adherent? With Crixivan, are you serious? But, I am probably in the 98 to 99 percent adherence level.

As has been pointed out, the virus does hide in some spots (lymph nodes, brain, central nervous system, anal secretions, etc.) Some drugs cross some of the barriers to reach some of these locations (AZT crosses the blood/brain barrier), but there will always be a reservoir somewhere where this little bugger will hide and do what come naturally for it.

There are so many variables it would be impossible for anyone to predict how long a regimen will last. Some people like myself seem to last a long time on the same cocktail. Others develop resistance even with 100 percent adherence.

All we can do is continue to fight as best we can, working with what we've got. Things have really improved since I started my regimen, I hope that continues and someday there is a breakthrough that may allow us to live normally and, as HIV worker said, without drugs.

Until then, I'll keep popping my pills, scheduling my meals around my pill times, keep monitoring my CD4s and viral loads and do whatever I can to enjoy life.

I agree with that last post, but add crude food for thought. Is the fact that you have to take three sets of drugs to potentially keep HIV at bay...at best "Bollocks"? The side effects, the adherence, the reminders of HIV? Therapy is failing the HIV positive community. No? It's far from crap, but it's also far from acceptable.

R

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Perfect adherence greatly extends the life span of an antiviral regimen, but it appears that most of us will develop some resistance at some point, regardless. The key seems to be holding it off as long as possible, while newer and better therapies are developed.

Which was supported by:

<< Most HIV physicians also have experience with patients who report the same faithfulness with the same regimen, only to experience virologic failure and resistance after months or years.

We have good evidence that virus evolution, with the development of resistance mutations, continues in the bloodstream and in 'sequestered sites' in the body such as the gonads and the central nervous system, even in patients with undetectable viral loads by standard viral load assays>>

I am trying to follow your train of thought here. It appears that you might be misinterpreting the intent of this statement: "HIV resistance is the near inevitable consequence of failure of antiretroviral drugs to fully suppress viral replication in treated patients." What it is saying is if an antiretroviral regimen fails to maximally suppress viral replication (i.e, viral load remains detectable above 50), then resistance is likely to happen. This is irrespective of what causes the treatment to fail to suppress the viral load to less than 50: it could be due to incomplete adherence (which could be from missing doses, or inability to take the meds due to side effects, or other reasons), it could be due to pre-existing acquisition of resistant strains that was not detected and have faded in the background and then re-emerged after the drugs were started, or in some situations, the regimen simply fails to suppress the viral load maximally in spite of perfect or near perfect adherence. Thus, it is the treatment failure that causes the subsequent development of resistance. On the flipside of it, individuals who are able to suppress the viral load maximally to <50 have the best chances of having a durable treatment response for many years for as long as they are able to tolerate and adhere to the regimen.

This is also in the same line as what was in this conclusion which you likewise quoted: "A Swedish group confirmed that resistance mutations do emerge among people with viral loads between 50 and 500 copies/ml (Soderborg 1999)." Remember that viral loads consistently above 50 (which includes the 50-500 range) in the setting of HAART actually do represent treatment failure. This is the reason why treatment success is gauged as achieving and maintaining viral loads at less than 50. So in the former setting (viral load range 50-500), there is in fact a greater chance of development of resistance to meds being taken compared to someone taking the exact same meds and who is able to keep the viral load consistently < 50.

Finally, you chose this quote from Dr. Sherer with his response to a similar question: "Most HIV physicians also have experience with patients who report the same faithfulness with the same regimen, only to experience virologic failure and resistance after months or years. We have good evidence that virus evolution, with the development of resistance mutations, continues in the bloodstream and in 'sequestered sites' in the body such as the gonads and the central nervous system, even in patients with undetectable viral loads by standard viral load assays."

In the interest of fairness and balance, I think we also need to present here the next paragraph of his response: "However, in spite of this evidence, we have many instances of prolonged successful suppression, like your case. Apparently ongoing evolution as I've described it does not inevitably lead to clinically significant viremia, resistance, and virologic failure. It may be that the low level development of resistant clones is adequately managed in some people by one or two of the active drugs in an active three drug regimen, in spite of the resistance to one of the drugs, as well as their immune system."

These articles were NOT suggesting that the emergence of resistance during antiretroviral treatment is inevitable and I hope that was not what you concluded from reading them (although it could easily be misinterpreted that way) nor that it was the message you were trying to convey.

Gerry

P.S. It also does not imply that just because a regimen fails and emergence of resistance develops that the reason for such is non-adherence. It is one of the things that can lead to treatment failure but is not by any means the only reason for it.

<<HIV resistance is the near inevitable consequence of failure of antiretroviral drugs to fully suppress viral replication in treated patients. >>

JK I'm not disputing that statement.

What the article author means by "fully suppress" (undetectable w/ ghastly reservoirs or low viral load low still above above 50 copies) is not clear from that article.

(Basically what I just noticed Gerry wrote above when I was about to post this.)

But building on HIV workers great insights, I do agree that there are a lot of unknowns. But from ten years of data comparing those who are strictly adherent and undetectable to those who aren't, the emergence of resistance is low.

Will it take 40 years or 30 years for some and eventual resistance even the most adherent and virologically suppressed? I guess we'll all know then. No way to know when all we have is ten years of data onHAART. But the odds for decades is good for many with little resistance and great adherence/suppression.

The important thing I take from all this is that adherence and vigilance is important. Also, that we should remain hopeful for better treatments on the horizon!

Ciao bellos and bellas!Mikey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

Good subject. I think fear of resistance is always in the back of our minds. I just go by those few I personally know, long term on meds. None have developed resistance having been on meds for 8 years to 10 years. And these latest drugs are better than ever before. So I guess why worry if you follow the directions. It may happen but doubtful for most. I try not to worry about things that could but havent happened. If you do, it can itself drive you nutz.

A study by Andrew Phillips, looked at results from resistance tests of people in London/Brighton who were using combinations of three of more drugs:

Between1996 and 2003, around 4,500 patients started combo with 3 or more drugs. Just over half started with an non-nuke (eg Sustiva), the rest with a protease inhibitor. The cumulative risk of virological failure (two viral loads of more than 1,000 after 24 weeks from start of combo) was 24% by 2 years, 34% by 4 years and 42% by 6 years.

Risks by 6 years for class-specific mutations were:

- M184V/I 18%,- 1 or more TAM 15%- Non-nuke 17% overall. BUT 25% for people who started with a non-nuke- PI 8% overall, 10% for people who started with a PI

Q: What does this mean then, newt?

0. Global figs, not very well developed in terms of adherence, length of infection etc.

1. M184 is the "classic" nuke mutation that leads to 3TC resistance. But this may not be that important treatment-wise, cos lots of other nukes are more effective against M184V strains, and it may be a preferable (eg more weedy) strain to have.....

2. Starting on Sustiva? That's a high chance of resistance. It takes no account of (a) adherence (b) pre-existing but undetected non-nuke resistance. I would like to see a more sophisticated (adherence controlled, genotype controlled) breakdown. Non-nuke resistance is usually sudden death. PI resistance is more subtle, rather like the gradual erosion of a cliff by the ocean. The PI nos are for 'old' combos ie nothing newer than Kaletra.

4. Life never matches the science. I have a colleague who religiously took hisSustiva/Combivir to the minute and got an across the board flat-out nuke + non-nuke resistance. And an older friend who's only ever done 3TC + 1 other nuke (1st ddI, now abacavir) and is happily undetectable and has been forever (since 1997). My ex got resistant to Sustiva after 2 1/2 yrs (cos it was tripping him out and he was skipping doses perhaps...) + some ddI resistance, but is undetectable on a PI + Truvada.

Hello,From my understanding and personal experience- yes. I am pretty much resistant to most of the meds, even with very close to 100% adherence. I eat well, don't do recreational drugs, don't drink, smoke, exercise...everything one is supposed to do to help, and I still have resistance. There are a small % of people who this happens to. It can be really frustrating.Christine

Is the fact that you have to take three sets of drugs to potentially keep HIV at bay...at best "Bollocks"? The side effects, the adherence, the reminders of HIV? Therapy is failing the HIV positive community. No? It's far from crap, but it's also far from acceptable.

R

Well, I do not think it is at best bollocks. We've yet to find the magic single drug that will wipe out HIV, but I am sure a lot better off then the thousands that died before the discovery of HAART.

The number of drugs does not bother me. I have a friend who is really excited about those combination pills that will combine three drugs in a pill he takes twice a day. Personally, my cocktail involved two prescriptions, 4 pills 2x/day. Adding that to the allergy meds, prostate meds, & ADs that I take everyday was not that hard to do. I hated the side affects. For me, I wish they'd concentrate on the side affects issue. Compare that to another friend of mine, been poz since 85, he's on a three drug regimen where only one med is actually working, the other two are just "holding back the floodwaters," says his doc. Lucas is in desperate need of a new class of drugs, I'd prefer that science find the new class for him before dealing with my side-affects issue.

I have a lot of confidence in the scientific community. They'll keep creating new classes of drugs, easier dosing of existing drugs and eventually will discover the holy grail, therapeutic and preventative vaccines.

I have gotten resistant to most of the available drugs, in spite of very good adherence.

My doc has always told me I have a very aggressive strain that mutates a lot.Still, I am undetectable since 1997 and on my current schedule for 1 year.

hermie

What does your doctor base that explanation on? Just the fact you have been taking meds and are resistant or do they actually have some evidence? I guess my question is, "Does he/she really know?

R

PS. Sorry about my writings last night. Not very professional.

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Question: For persons who are trying treatment now for the first time with at least a 250 t-cell count, how long does a drug regimen usually last before becoming drug resistant? two years? 5 years? 10 years? longer? Thanks for your answer.

Patients who remain optimally adherent to a well chosen (by baseline resistance testing) HAART regimen have a greater than 90-95% of having success. Adherence is much more important than baseline CD4 counts (at least in this range) in predicting the rate of treatment failure or drug resistance.

For patients who have viral suppression after the first year of treatment, it's very, very rare to see failure and resistance in subsequent years. BY

It was good to see another confirmation of what I've been told numerous times by my doctors. Always verify!!!!

Ciao!!!!MIkey

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"Get your medical advice from Doctors or medical professionals who you trust and know your history."

"Beware of the fortune teller doom and gloomers who seek to bring you down and are only looking for company, purpose and validation - not your best physical/mental interests."

"You know you all are saying that this is incurable. When the real thing you should be saying is it's not curable at the present time' because as we know, the great strides we've made in medicine." - Elizabeth Edwards

It all started when I first got on meds in 1995.I remember I first got on AZT. after about one year that therapy failed, although I never missed a dose.On the next one I got a toxic hepatitis and had to switch.After having stopped for several weeks I started again, and had to switch several times again.Sustiva made me act like a mad man.

What I mean is that I would have to ask what evidence they have for the mutations. But I know there is some.And I always heard : you have a very aggressive strain that constantly mutates.

When you are really interested I can ask for my files.

Hermie

Hermie

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Diagnosed in 1987 and still kickingViread, Kivexa (Epzicom),Viramune once daily

If one goes back to the original question "Can resistance still occur even with 100% adherence?" this can easily be answered with a yes. This is partly because not all regimens will be successful in suppressing the viral load down to undetectable (<50). So for those who continue to have detectable viral loads in spite of being adherent to a drug regimen, then there is a possibility of developing resistance down the road. The more difficult thing to answer is how long one can expect a particular regimen to be successful in keeping the viral load to <50, which offers the best chances of not developing resistance. This is of course due to several reasons, the most obvious of which is we only have 10 years of HAART history to rely on. Even with that 10 year history; there is a big difference between HAART in the earlier years and HAART in the later ones. Other factors include the heterogeneity of individuals going on HAART (some are treatment naive, while some are treatment experienced), and the multiple combinations of drugs that have become available. Therefore, epidemiologic studies in the so-called HAART era such as the one provided by Matt (thanks Newt!) is applicable only for the time frame that the data is collected.

For instance, the report by Pillips which observed 4500 patients in the UK from 1996 to 2003 and calculated the risk of treatment failure to be 24% by 2 years, 34% by 4 years and 42% by 6 years is quite sovering. But this does not mean that one will see a similar picture if they looked at another cohort that just started ARV's say beginning from 2000 to the present. In other words, past performance is not a guarantee of future results.

Take for instance the GS903 trial which started in 2000 and was one of the studies that got Viread approved. Patients in the Viread/3TC/Sustiva treatment arm (in Brazil, Argentina and the Dominican Republic) were observed for an additional 2 years after the first 2 years of the trial were concluded. At the 4 year mark, the proportion of patients with VL < 400 was 95% by on-treatment analysis and 91% by intent-to-treat (missing = faililure analysis); the proportion of patients with VL < 50 was 92% by on-treatment analysis and 87% by intent-to-treat (missing = failure analysis). Granted that this has a much smaller sample size (86), but this gives a much more different picture from the 34% failure rate by year 4 quoted in the epidemiologic study above.

Clearly the answer is yes. Resistance develops even with 100% compliance.

This underlines the point that current treatments are not a cure. Just a method of management for a set period of time. HIV infection is still ultimately a fatal condition for the vast majority of us who have it.

I do not doubt that there are HIV mutations that bear resistance. What I am wondering is about this highly mutating strain. I am not doubting that it is possible, but I was wondering if they had any evidence other than the resistance occured even with strict pill-taking. It does occur, but in order to study why HAART fails requires an understanding as to why. I've heard of highly mutating strains but not really seen the evidence. To be so would require mutations in RT that make it more sloppy or a strain that can replicate better in places HAART can't currently go. My motivation was to ask what evidence your doctor gave you, if any, as this might help improve HAART therapy.

R

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

I am concerned about the necessity for insisting that adherence will always equal success. Not only does that set up a patient for self-reproach in the event that resistance occurs, it sets a precedent in the HIV community where getting sick becomes "your own fault." That's not optimism. That's elitism.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

I am concerned about the necessity for insisting that adherence will always equal success. Not only does that set up a patient for self-reproach in the event that resistance occurs, it sets a precedent in the HIV community where getting sick becomes "your own fault." That's not optimism. That's elitism.

I understand your concern. May I ask what advice you would give someone who has never been on treatment and who is about to start treatment?

I would suggest that they examine not only the drugs, but the life into which a drug regimen is about to be inserted. As it stands, these drugs are to be taken on time, every day, for the rest of a person's life. Until and unless a person truly feels ready for this committment, side effects and all (the long term side effects are only now beginning to surface) then they absolutely must not be bullied into drug therapy.

A social network, either on or offline, where the person can present any potential problems and discuss side effects, adherence, et al without fear of recrimination is vital. It is my firm belief that this site can provide part of that, for those who seek it. But only if we do not gloss over the negative aspects in our zeal to provide optimistic support.

Support which ignores factual data is a lie. And such a monumental decision should never be based on a lie. If this scares someone, I am sorry about that. HIV is a scary disease. One of the scariest. Being scared is not only understandable, it is the normal response to such a life-altering situation. Thing is, to provide the information AND the support in such a way that a person can make up his/her mind about when the time is right --- if ever --- to start, change, stop, or resume treatment.

But it's my opinion that setting people up to fail by withholding or ignoring evidence is not being supportive. And neither is the insinuation that drug resistance is a patient's fault. HIVWorker spoke quite eloquently regarding this topic, and the actual experiences of people like Moffie, Joe, and others.

These drugs, when used optimally, often work miracles. But sometimes they fail. And sometimes they fail regardless of adherence. Why am I being a pessimist when I state that simple fact? Without locking patients up and monitoring their adherence, we have only patient report combined with lab/primate study to base our percentages on. And that's close to conjecture, albeit learned conjecture.

Would I suggest that a person learn all they can, not only about their drugs but about their disease, before starting treatment? Absolutely. And sometimes part of that education is discerning when a person is ready to make that committment, and what boundaries they are going to establish. Do they switch drugs which suppress viral replication because these drugs also cause facial wasting or fat redistribution? Do they change or stop meds because the emotional side effects render them paranoid or suicidal? Do they stop or change treatment because of the relentless diahrrea? Everyone has a breaking point, a point at which they can not cross without losing the very will to thrive that HAS to be in place to motivate a successful regimen.

So what do I recommend? A lot of soul searching. Because once committed, the risk of resistance becomes very real if decisions are reversed. That should be scary. This is scary stuff.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

The other thing that bothers me in all of this is that doctors frequently claim that resistance to HIV medication even with 100% compliance is due to that person being infected with a "Highly mutating" strain of HIV. In the absence of data, this explanation is mere hand-waving. While it is a definite possibility, it is also possible that the particular drug combination that the person was on was defective for reasons of PK in that individual. Claiming the virus is "highly active" or "Aggressive" might lead to the person thinking that NO drug combination will work for them. In the absence of clear data that this is the case it seems to me a pretty unfair thing to claim. Why blame the virus when it could be the specific treatment that is at fault. While personal PK issues can not be predicted prior to giving any drug and therefore can not dictate therapy, to throw the hands in the air and claim the virus is aggressive because it didn't work seems a little short-sighted.

R

« Last Edit: June 08, 2006, 10:48:02 AM by HIVworker »

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Without locking patients up and monitoring their adherence, we have only patient report combined with lab/primate study to base our percentages on. And that's close to conjecture, albeit learned conjecture.

JK, could you expound on what you mean by this? Are you saying that the studies that try to explore adherence in relation to treatment success or failure are inaccurate? Please clarify. Thanks.

<< Are you saying that the studies that try to explore adherence in relation to treatment success or failure are inaccurate? Please clarify. >>

I am sorry I did not expand on this. I was saying that patient report, in the absence of monitoring, is soft data. I realize that there are monitoring devices which can be affixed to pill bottles and trays, which could deliver information about when the bottle was opened, etc. These studies carry far more weight with me than patient report alone.

However, I have yet to see the science behind a "90% success rate" if adherence is present. Could you possibly provide this data?

More to the point (well, HIVWorker's point really) what qualifies as success? Undetectable viral load? Patient quality of life? The absence of OIs? Rising CD4 count? Percentages?

I truly despise being in the position of board downer here. My vote is for a realistic look at the state of our medical art, and participation in that practice as a patient with all available information, not only the convenient or happy facts.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

Please do. I just want to know whether they have any evidence that you have a highly mutatable strain.

JK

As ever you bring up a good point and one I am keen to get more data about. I mean keeping viral load down without mutations. I echo your point though. Current therapy, while better than nothing, is far from viable. If HIV medication was able to keep the viral load down in an acceptable manner, then this forum wouldn't have a whole section dealing with side effects. Clearly this is an area that urgently requires action. It is not surprising, perhaps, that there are so many side effects because for one there are so many drugs to take at the same time. There is a world of difference between keeping the virus at bay and improving quality of life. I would like to hear what other people think...

I would also love to hear more on what people DONT like about current therapy.

R

« Last Edit: June 08, 2006, 10:40:27 PM by HIVworker »

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

If you are asking about studies on adherence and “treatment success,” this study is one of the most commonly quoted studies that gave rise to the desirable 95% adherence rate. The virologic failure was defined as VL>400. In this study, even at the 95% adherence rate, virologic failure was still at 22%, but 80% of those with less than 80% adherence experienced virological failure at 6 months. The point being emphasized in studies such as this is that as adherence declines (for whatever reason), virologic failure increases. But this only addresses the relationship of adherence to virologic failure. It does not provide a direct link to emergence of drug resistance or its quantification. This review article discusses other aspects that come into play as far as emergence of resistance is concerned including potency of the regimen, adherence, tolerance, genetic and pharmacologic barriers to development of resistance, and transmission of resistant strains.

As to your other question as to what qualifies as success, I guess that will really depend on the individual, and would certainly be influenced by a lot of factors, including experience with drug treatment. Here’s another article that explores factors that influence some long-termers’ decision-making on ART.

It’s probably prudent to not dismiss studies based on patient reports as “soft data” particularly if the conclusions being arrived at are pretty consistent. If you do, you run the risk of creating a cloud of suspicion on the very data that you present when you try to make your case regarding HIV transmission risks because a lot of these studies are, after all, also based on patient self reports.

<<, If you do, you run the risk of creating a cloud of suspicion on the very data that you present when you try to make your case regarding HIV transmission risks because a lot of these studies are, after all, also based on patient self reports>>

For the record, I DO emphasize transmission data that relies upon more concrete information than post-infection patient reports. Moreover, the romero and other serodiscordant studies actualyl utlilize methodology which makes the common pitfalls of patient self-report work in favor of, not against, the collection of accurate data.

While I do not dismiss patient report studies entirely, I am constantly reminded that the plural of anecdote is not data. Patient report is notorious in it's unreliability. And when patient report flagrantly disputes other scientific methodology (e.g. laboratory study and primate/simian research) I am very skeptical, especially considering the controversial issues of sexuality and a virtually unheard-of required level of drug-regimen adherence.

There are three studies using serodiscordant couples I tend to use almost exclusively in order to asertain transmission rates, as they provide the hardest data. Say what you want about my scientific abilities, I am consistent.

The salient point of this thread, and my participation in it, is to emphasize that adherence is absolutely vital in order to achieve sccessful therapy. But in time, given the mutating quality of the virus and the body's long-term response to the drugs, it is estimated that many if not most first-line treatments will ultimately fail. Whether this happens in months, years, or decades seems to be the sticking point that scientists are attempting to asertain.

<< In this study, even at the 95% adherence rate, virologic failure was still at 22%, but 80% of those with less than 80% adherence experienced virological failure at 6 months.>>

Which was my point precisely. Not trying to scare ANYONE with this data, but it's important to know where we are, and are not, in the field of HIV research and medicine. We are staying alive for decades longer than anyone ever thought we would, thanks in large part to HAART. However, we only have perhaps fifteen year's worth of data to go by. And from the poignant and heartfelt postings made by (often dismissed or ignored) old-timers, these fifteen years have often come with a tremendous price in dignity, financial security, and even quality of life. These things should neither be dismissed nor ignored in favor of blind optimism. Such an approach, in my opinion, is not support. It is mutual deception and denial, and ultimately it casts out those who have the most experience and wisdom to offer newly diagnosed/newly treated people.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

"The salient point of this thread, and my participation in it, is to emphasize that adherence is absolutely vital in order to achieve sccessful therapy."

This is something we can definitely agree on, and by "successful therapy" I'm assuming you mean maximum viral suppression

But in time, given the mutating quality of the virus and the body's long-term response to the drugs, it is estimated that many if not most first-line treatments will ultimately fail. Whether this happens in months, years, or decades seems to be the sticking point that scientists are attempting to asertain.

I don't think scientists have even ascertained that the first sentence of your statement here is true, especially in the subgroup of individuals who do not harbor resistant strains, who started HAART in the latter half of the last decade, who are able to tolerate the meds and who are able to follow your first statement above ("adherence is absolutely vital in order to achieve successful therapy")

And from the poignant and heartfelt postings made by (often dismissed or ignored) old-timers, these fifteen years have often come with a tremendous price in dignity, financial security, and even quality of life. These things should neither be dismissed nor ignored in favor of blind optimism.

Agreed. And it is just as important not to dismiss the favorable results achieved by others with their treatment, including several long-termers, as just an illusion. They are just as real as others' experiences.

HAART is not the ultimate answer to HIV, but its the only thing we've got at the moment for those who are lucky enough to have access to it. And while we are trying to desperately wait for the next breakthrough, we need to make the most of what we've got. That's all I'm saying.

<<Agreed. And it is just as important not to dismiss the favorable results achieved by others with their treatment, including several long-termers, as just an illusion.>>

I have not done this. Will not do this. Will not ever do this. And as I mentioned before, despise being put into the position of defending a point of view which even implies this.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

While it is certainly possible for resistance to occur, I think that it is far better to maintain 100% adherence (or at least as close as possible) and keep hope alive that the virus either doesn't develop resistance or that it at least takes while before it does. I have been on Sustiva and Combivir since Sept. of 2000 and have managed to keep my viral load non-detectable from the beginning. So far there is no sign of resistance, minimal side effects, and no liver damage from the toxic nature of the drugs.

Justin, steering clear of the meds because of potential side effects and eventual resistance is a little like not dating until you have planned the wedding. Nothing lasts forever, or works perfectly. And not everyone has the same experience.

The key is to stay alive until the next breakthrough. And then the next. and then the next.

I understand what you mean by surviving until the next breakthrough....which is why I am not against taking meds....just a lil afraid.

Hmm not dating until I have planned the wedding?!.....does it count that I have already planned the perfect wedding when I was a kid....but I am still not dating as of yet.

My doctors says that resistance happens when you don't adhere to your regimen. Also a lot of people they see in the clinic meds are working fine, then get reinfected with another strain of HIV from continuing to have unprotected sex and then then drugs they currenty take don't seem to work for the new HIV strain they aquired.

My doctors says that resistance happens when you don't adhere to your regimen.

It's actually not the case. I wasn't resistant to any meds when I started my first regimen. In less than 8 months I became resistant to Ziagen ( abacavir ) and was 100% adherent...never missed a dose and all took in time.

Interesting. Because there are less than two dozen confirmed cases of reinfection on record, and scientists postulate that reinfection is most likely in the months directly after initial infection, before the dominant strain asserts itself. Perhaps all these cases were/are from the same clinic?

Insofar as adherence is concerned, it is vital for a successful regimen. But to postulate that resistance automatically equals a lack of adherence is a gross misinterpretation of the science and the epidemiology. It also stigmatizes a patient as non-compliant when there is NO proof of such.

I am continually shocked at how stupid doctors think we patients are. How often they "dumb down" information until it is essentially worthless, and certainly inaccurate. Or perhaps these doctors are not as well versed in the latest medical studies as they purport to be? I don't know, and really don't care much. In the end, its the uninformed patient (or the patient who trusts his healthcare provider without verification) who suffers.

Trust, but verify. The science, the truth, is out there in first tiered peer-reviewed scientific journals. The facts about resistance and reinfection and all sorts of other potential pitfalls which can beset HIV infected people are better and better understood every day. We as patients owe it to ourselves to do that research necessary to make important life decisions.

Even if it means ultimately changing incompetant or condescending doctors.

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

That's funny the VA Medical Center and the Naval Medical Center both passed this information to me that that is one reason why they have drug failures. I tend to listen to the doctors and specialist, I don't think that make things up. That is my opinon but everyone can have there own.

Again...beleive what you want...these are all opinons. I never said that one cannot become resistant other than the two ways I have described. Only that these are the issues they are dealing with at the Military and Veterans Infectious disease clinics. I know everyone is not alike...people become resistant even when they do everything they can. These are two things people can do to have peace of mind that they did there part...adherence and protected sex. Enough said. I'm done.

My doctors says that resistance happens when you don't adhere to your regimen.

and I gave you facts that resistance can occur when you adhere to your regimen, that's all. You statement sounded like you can't developped resistance when adhering to your regimen, and it's not my reality.